Shape-versatile fixed cellular materials for multiple target immunomodulation

Abstract

Therapeutic cells are usually administered as living agents, despite the risks of undesired cell migration and acquisition of unpredictable phenotypes. Additionally, most cell-based therapies rely on the administration of single cells, often associated with rapid in vivo clearance. Three-dimensional cellular materials may be useful to prolong the effect of cellular therapies and offer the possibility of creating structural volumetric constructs. Here, we report the manufacturing of shape-versatile fixed cell-based materials with immunomodulatory properties. Living cell aggregates with different shapes (spheres and centimeter-long fibers) were fixed using a method compatible with maintenance of structural integrity, robustness, and flexibility of three-dimensional constructs. The biological properties of living cells could be modulated before fixation, rendering an in vitro anti-inflammatory effect towards human macrophages, in line with a decreased activation of the NF-κB pathway that preponderantly correlated with the surface area of the materials. These findings were further corroborated in vivo in mouse skin wounds. Contact with fixed materials also reduced the proliferation of activated primary T lymphocytes, while promoting regulatory populations. We propose the fixation of cellular constructs as a versatile phenotypic stabilization method that can be easily implemented to prepare immunomodulatory materials with therapeutic potential.